Bisphenol A regulates the estrogen receptor alpha signaling in developing hippocampus of male rats through estrogen receptor.

Bisphenol A (BPA), one of the most common environmental endocrine disruptors, has been recognized to have wide adverse effects on the brain development and behavior. These adversities are related to its ability to bind estrogen receptor (ER) with subsequent alteration of its expression in the target areas. However, very little is known about whether BPA exposure also affects ER phosphorylation and its translocation to nucleus during postnatal development, two critical steps for its function. Here, we found that during development from postnatal day 7 (P7) to P21, the alpha subtype of ER (ERα) in the hippocampus of male rats experienced remarkable alterations in terms of its expression, phosphorylation and translocation to nucleus. Exposure to low level of BPA had bidirectional, development-dependent effects on the expression of ERα mRNA and protein, but decreased ERα phosphorylation and impaired its translocation to nucleus throughout the period investigated. Treatment with low dose of ICI 182,780 (ICI), an ER antagonist to block the binding of ER with BPA, reversed the altered ERα following BPA exposure, highlighting critical involvement of ER. Moreover, ICI treatment rescued the hippocampus-dependent behavioral deficits in the adult rats experiencing early-life BPA exposure. Overall, our results indicate that BPA interferes with the ERα signaling in the developing hippocampus in an ER-dependent manner, which may underlie its adverse behavioral and cognitive outcomes in adult animals.

The effects of perinatal bisphenol A exposure on thyroid hormone homeostasis and glucose metabolism in the prefrontal cortex and hippocampus of rats.

INTRODUCTION: Bisphenol A (BPA) is an endocrine disruptor widely used to manufacture consumer goods. Although the thyroid hormone (TH) disrupting potential of BPA has been thought to be responsible for the neuropsychiatric deficits in the animals that experienced perinatal BPA exposure, the TH availability change at the level of specific brain structures has not been subject to systematic investigation. METHODS: In the present study the impacts of perinatal BPA exposure (0.1 mg/L in drinking water) spanning gestation and lactation on TH homeostasis in the prefrontal cortex (PFC) and hippocampus were assessed in male Sprague-Dawley rats at postnatal day 21 (PND21) and PND90. As TH regulates brain glucose metabolism at multiple levels，the effects of BPA treatment on glucose metabolism in the brain tissues were also assessed in adult rats. RESULTS: The results showed heterogeneous changes in TH concentration induced by BPA between serum and brain tissues, additionally, in the BPA-treated pups, up-regulated expression of the TH transporter monocarboxylate 8 mRNA at PND21 and increased type 3 iodothyronine deiodinase mRNA expressions at PND21 and PND90 were observed. Meanwhile, decreased glucose metabolism was seen in the PFC and hippocampus, while deficits in locomotor activity, spatial memory and social behaviors occurred in BPA-treated groups. CONCLUSION: These data support the concept that the developing brain possesses potent mechanisms to compensate for a small reduction in serum TH, such as serum hypothyrodism induced by BPA exposure, however, the long-term negative effect of BPA treatment on TH homeostasis and glucose metabolism may be attributable to neuropsychiatric deficits after mature.